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Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

One hundred thirteen investigators in 21 countries participated in this study.

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

In total 1092 participants were screened, of which 590 participants were randomly assigned and treated (294 participants were treated with DRV/rtv 800/100 mg once daily, and 296 participants with DRV/rtv 600/100 mg twice daily.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Virological Response at Week 48 (Number of Participants With Plasma Viral Load Less Than 50 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm

Measure Description

The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.

Time Frame

48 Weeks

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intention To Treat (ITT) population: Participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if preceeding and succeeding visits indicated response. Otherwise, intermittent values were imputed with nonresponse.

Virological Response at Week 48 (Number of Participants With Plasma Viral Load Less Than 50 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm [Units: Participants]

212

210

Statistical Analysis 1 for Virological Response at Week 48 (Number of Participants With Plasma Viral Load Less Than 50 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm

Groups [1]

All groups

Statistical Test Type [2]

Non-Inferiority or Equivalence

Statistical Method [3]

Regression, Logistic

P Value [4]

<0.001

Difference in proportion of response [5]

0.0019

95% Confidence Interval

-0.054 to 0.092

Standard Error of the mean

(0.037)

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

Assuming a response rate of 70% at 48 weeks for both treatment groups, 306 participants were required per treatment arm to establish noninferiority of darunavir (DRV)/ritonavir (rtv) once daily versus DRV/rtv twice daily with a maximum allowable difference of 12%, with a 1-sided significance level of 0.025 and 90% power.

[2]

Details of power calculation, definition of non-inferiority margin, and other key parameters:

If at Week 48, the lower limit of the 95% two-sided confidence interval of the difference between DRV/rtv once daily and DRV/rtv twice daily exceeds -12%, non-inferiority of the DRV/rtv q.d. versus the DRV/rtv b.i.d. therapy was concluded.

[3]

Other relevant method information, such as adjustments or degrees of freedom:

The model includes treatment as factor and baseline viral load (log10) as covariate.

[4]

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

Area Under the Curve From the Time of Study Medication Administration Upto 24 Hour Postdose (AUC24h) of DRV and Rtv [ Time Frame: 0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48. ]